Biochem/physiol Actions

AZD3839 is a potent and selective BACE1 inhibitor (Ki = 26.1 nM/BACE1, 372.4 nM/BACE2, >25 µM/Cathepsin D by cell-free TR-FRET; hERG IC50 = 4.8 µM) that effectively suppresses cellular BACE1 activity in neuron cultures (sAPPβ release IC50 = 16.7 nM/SH-SY5Y; Aβ40 release IC50 = 4.8 nM/SH-SY5Y AAP695wt, 32.2 nM/N2A, 24.8 nM/guinea pig cortical neurons, 51 nM/murine cortical neurons) and exhibits in vivo Aβ40-, Aβ42-, sAPPβ-reducing efficacy (80 & 160 µmol/kg mouse, p.o.; 100 & 200 µmol/kg guinea pigs, p.o., 2.5 & 20 µmol/kg cynomolgus monkeys, i.v.) with good pharmacokinetic properties and oral availability.